U.S. patent application number 10/532284 was filed with the patent office on 2005-11-17 for preparation of substituted indenes.
This patent application is currently assigned to Basell Polyolefine GmbH. Invention is credited to Fisch, Lothar, Schottek, Jorg, Schulte, Jorg.
Application Number | 20050256344 10/532284 |
Document ID | / |
Family ID | 32178273 |
Filed Date | 2005-11-17 |
United States Patent
Application |
20050256344 |
Kind Code |
A1 |
Schulte, Jorg ; et
al. |
November 17, 2005 |
Preparation of substituted indenes
Abstract
The present invention relates to a simple process for preparing
specifically substituted indenes of the formula (I) or (Ia) 1 to
compounds of the formula (II) serving as starting materials 2 and
to the use of the compounds of the formula (II) as starting
materials for the synthesis of substituted indenes.
Inventors: |
Schulte, Jorg; (Frankfurt,
DE) ; Schottek, Jorg; (Frankfurt, DE) ; Fisch,
Lothar; (Kelkheim, DE) |
Correspondence
Address: |
CONNOLLY BOVE LODGE & HUTZ, LLP
P O BOX 2207
WILMINGTON
DE
19899
US
|
Assignee: |
Basell Polyolefine GmbH
Frankfurt Am Main
DE
65926
|
Family ID: |
32178273 |
Appl. No.: |
10/532284 |
Filed: |
April 21, 2005 |
PCT Filed: |
October 18, 2003 |
PCT NO: |
PCT/EP03/11585 |
Current U.S.
Class: |
568/734 ;
260/665G |
Current CPC
Class: |
C07C 1/326 20130101;
C07C 2602/08 20170501; C07C 1/24 20130101; C07C 29/38 20130101;
C07C 17/14 20130101; C07C 29/38 20130101; C07C 1/24 20130101; C07C
17/14 20130101; C07C 17/208 20130101; C07C 17/208 20130101; C07C
1/326 20130101; C07C 13/465 20130101; C07C 22/04 20130101; C07C
35/32 20130101; C07C 22/04 20130101; C07C 13/465 20130101 |
Class at
Publication: |
568/734 ;
260/665.00G |
International
Class: |
C07C 039/12; C07F
003/02 |
Claims
1. A process for preparing substituted indenes of the formula (I)
15and their double bond isomers of the formula (Ia) 16which
comprises converting a compound of the formula (II) 17into a
bisorganometallic compound of the formula (III) 18and reacting this
with a compound of the formula (IV) 19to give an indanol of the
formula (V) 20and converting this into an indene of the formula (I)
or (Ia) by elimination of water, wherein the compound of the
formula (II) 21is prepared by coupling of a compound of the formula
(VI) 22with a compound of the formula (VII) R.sup.2--X.sup.2 (VII)
in the presence of a transition metal catalyst, with either the
compound of the formula (VI) or the compound of the formula (VII)
firstly being converted into a corresponding organo-metallic
compound, and the coupling product of the formula (VIII) 23is
reacted with a halogenating agent to give a compound of the formula
(II), where R.sup.1 is a linear, branched or cyclic
C.sub.1-C.sub.10-alkyl radical, R.sup.2 is a substituted or
unsubstituted C.sub.6-C.sub.18-aryl radical selected from the group
consisting of phenyl, 1-naphthyl, phenanthryl, 3-tert-butylphenyl,
4-tert-butylphenyl, 3,5-di(tert-butyl)phenyl, 4,4'-biphenyl and
3,5-di(phenyl)phenyl, R.sup.3-R.sup.5 are each hydrogen, X is a
chlorine atom, X.sup.1 is halogen, X.sup.2 is halogen, M is
magnesium monochloride and, Y is OR.sup.6, where R.sup.6 is a
linear, branched or cyclic C.sub.1-C.sub.10-alkyl radical.
2. A compound of the formula (II) 24where R.sup.2, R.sup.3,
R.sup.4, R.sup.5 and X are defined in claim 1.
3. The use of a compound of the formula (II) as claimed in claim 2
as starting material for the synthesis of substituted indenes of
formula (I) or (Ia) as defined in claim 1.
4. The process of claim 1 wherein X.sup.1 is chlorine, bromine or
iodine and X.sup.2 is chlorine, bromine or iodine.
5. The process of claim 4 wherein X.sup.1 is chlorine and X.sup.2
is bromine.
Description
[0001] The present invention relates to a simple and efficient
process for preparing specifically substituted indenes of the
formula (i) or their double bond isomers of the formula (Ia) 3
[0002] to compounds of the formula (II) serving as starting
materials 4
[0003] where
[0004] R.sup.1 is a C.sub.1-C.sub.40-hydrocarbon radical,
[0005] R.sup.2 is a substituted or unsubstituted
C.sub.6-C.sub.40-aryl radical, where the substituents of this aryl
radical are hydrocarbon radicals which contain no hydrogen atoms in
a positions relative to aromatic radicals or vinylic groups,
[0006] R.sup.3-R.sup.5 are identical or different and are each
hydrogen or a C.sub.1-C.sub.40-hydrocarbon radical which contains
no hydrogen atoms in a positions relative to aromatic radicals or
vinylic groups, or R.sup.2 together with R.sup.3 forms a cyclic
system, and
[0007] X is a halogen atom,
[0008] and also to the use of the compound of the formula (II) as
starting material for the synthesis of substituted indenes.
[0009] Substituted indenes are important intermediates for the
preparation of active compounds in the fields of pharmacy (Negwer,
VCH 1987, p. 1703 ff.), crop protection, fine chemicals, liquid
crystals and metallocene catalysts for the polymerization of
.alpha.-olefins (Chem. Rev. 2000, number 4).
[0010] Substituted indenes can be used to prepare chiral
ansa-metallocenes which are of great importance as transition metal
components of highly active catalysts for stereospecific olefin
polymerization.
[0011] Variation of the ligand system, for example by substitution,
enables the catalyst properties to be influenced in a targeted way.
This makes it possible to alter the polymer yield, the molecular
weight distribution, the tacticity and the melting point of the
polymers to the desired degree (Chem. Rev. 2000, number 4). Bridged
zirconocenes containing, as .pi. ligands, indenyl radicals which
bear the bridge in position 1, preferably a hydrocarbon radical, in
particular an alkyl radical, in position 2 and a further
hydrocarbon radical, in particular a substituted or unsubstituted
aromatic, in position 4 have been found to be particularly highly
active and stereoselective catalyst systems, as described in U.S.
Pat. No. 5,770,753 and U.S. Pat. No. 5,723,640. The ligand systems
used for these highly active metallocenes are prepared from the
corresponding substituted indenes.
[0012] The costs of preparing the indenes required for the
metallocene synthesis represent an important part of the total cost
of the metallocene synthesis. Various processes for the preparation
of 2-alkyl-4-aryl-substituted indenes have been described, for
example in U.S. Pat. No. 5,770,753, U.S. Pat. No. 5,723,640, WO
98/40331 and U.S. Pat. No. 5,789,634. The aryl radical in the 4
position is generally introduced by means of an aryl-aryl coupling
catalyzed by transition metals either immediately at the beginning
of the synthetic sequence or only after the indanone or indenyl
framework has been built up. In the abovementioned processes, the
alkyl radical in the 2 position on the indenyl framework is always
introduced before the 1-indanone system has been built up.
Organometallics 1993, 12, 4391-4401, describes the synthesis of
bisindenyl metallocenes which are bridged in the 2 position and are
unsubstituted on the six-membered ring and in which the two indenyl
ligands which are bridged in the 2 position are built up directly
by reaction of the bis-Grignard of
.alpha.,.alpha.-dichloro-o-xylene with an appropriate bridging
reagent. Organometallics 1999, 18, 4147-4155, describes the
synthesis of indenes which are substituted in the 2 position by
bulky aryl radicals and are unsubstituted on the six-membered ring,
likewise by reaction of the bis-Grignard of
.alpha.,.alpha.-dichlor- o-o-xylene with an appropriately
substituted methyl benzoate.
[0013] The syntheses known hitherto for preparing 2-alkyl-4-aryl-
or 2-alkyl-7-aryl-substituted indenes with varying 2 position on
the indenyl system of ansa-metallocenes and fixed substituents in
the 4 or 7 position on the indenyl system are still too
time-consuming and thus too costly.
[0014] It is an object of the present invention to find a simple,
flexible, quick and inexpensive process for preparing substituted
2-alkyl-4-arylindenes or 2-alkyl-7-arylindenes which avoids the
disadvantages of the known processes and allows, in particular, the
radicals in the 2 position on the endenyl system to be varied in a
simple manner.
[0015] We have found that this object is achieved by a process for
preparing substituted indenes of the formula (I) 5
[0016] and their double bond isomers of the formula (Ia) 6
[0017] which comprises converting a compound of the formula (II)
7
[0018] into a bisorganometallic compound of the formula (III) 8
[0019] and reacting this with a compound of the formula (IV) 9
[0020] to give an indanol of the formula (V) 10
[0021] and converting this into an indene of the formula (I) or
(la) by elimination of water,
[0022] where
[0023] R.sup.1 is a C.sub.1-C.sub.40-hydrocarbon radical,
[0024] R.sup.2 is a substituted or unsubstituted
C.sub.6-C.sub.40-aryl radical, where the substituents of this aryl
radical are hydrocarbon radicals which contain no hydrogen atoms in
a positions relative to aromatic radicals or vinylic groups,
[0025] R.sup.3-R.sup.5 are identical or different and are each
hydrogen or a C.sub.1-C.sub.40-hydrocarbon radical which contains
no hydrogen atoms in a positions relative to aromatic radicals or
vinylic groups, or R.sup.2 and R.sup.3 together form a cyclic
system which contains no hydrogen atoms in a positions relative to
aromatic radicals or vinylic groups, or R.sup.2 together with
R.sup.3 forms a cyclic system,
[0026] X is a halogen atom,
[0027] M is lithium, sodium, potassium or magnesium monohalide or
two radicals M together represent one magnesium atom, and
[0028] Y is a nucleophilic leading group.
[0029] Furthermore, we have found compounds of the formula (II)
11
[0030] where R.sup.2, R.sup.3, R.sup.4, R.sup.5 and X are each as
defined above, and also the use of these compounds as starting
materials for the synthesis of substituted indenes.
[0031] R.sup.1 is, for example, a C.sub.1-C.sub.20-alkyl radical, a
C.sub.6-C.sub.18-aryl radical, a C.sub.7-C.sub.40-arylalkyl radical
or a C.sub.7-C.sub.40-alkylaryl radical. R.sup.1 is preferably a
C.sub.1-C.sub.20-alkyl radical, in particular a linear, branched or
cyclic C.sub.1-C.sub.10-alkyl radical.
[0032] R.sup.2 is a substituted or unsubstituted
C.sub.6-C.sub.40-aryl radical, where the substituents of this aryl
radical are hydrocarbon radicals which contain no hydrogen atoms in
a positions relative to aromatic radicals or vinylic groups.
R.sup.2 is preferably a substituted or unsubstituted
C.sub.6-C.sub.18-aryl radical such as phenyl, 1-naphthyl,
phenanthryl, 3-tert-butylphenyl, 4-tert-butylphenyl,
3,5-di(tert-butyl)phenyl, 4,4'-biphenyl or
3,5-di(phenyl)phenyl.
[0033] R.sup.3-R.sup.5 are identical or different and are each
hydrogen or a C.sub.1-C.sub.40-hydrocarbon radical which contains
no hydrogen atoms in a positions relative to aromatic radicals or
vinylic groups. Examples of such hydrocarbon radicals are
tert-butyl, tert-pentyl, 1-adamantyl, phenyl, 1-naphthyl,
phenanthryl, 3-tert-butylphenyl, 4-tert-butylphenyl,
3,5-di(tert-butyl)phenyl, 4,4'-diphenyl and 3,5-di(phenyl)phenyl.
R.sup.3-R.sup.5 are preferably hydrogen.
[0034] The radicals R.sup.2 and R.sup.3 may together form a cyclic
system which contains no hydrogen atoms in a positions relative to
aromatic radicals or vinylic groups, with R.sup.2 and R.sup.3
together with the atoms connecting them particularly preferably
forming a substituted or unsubstituted 1,3-butadiene-1,4-diyl
group. Particular preference is given to R.sup.2 and R.sup.3
together with the atoms connecting them forming an unsubstituted
1,3-butadiene-1,4-diyl group.
[0035] X is a halogen atom such as chlorine, bromine or iodine, and
is preferably chlorine.
[0036] M is preferably magnesium monochloride.
[0037] Y is a nucleophilic leaving group such as halogen, an
R.sup.6CO.sub.2 radical or an OR.sup.6 radical. Y is preferably an
OR.sup.6 radical, where R.sup.6 is a C.sub.1-C.sub.40-hydrocarbon
radical such as a C.sub.1-C.sub.20-alkyl radical, a
C.sub.6-C.sub.18-aryl radical, a C.sub.7-C.sub.40-arylalkyl radical
or a C.sub.7-C.sub.40-alkylaryl radical. R.sup.6 is preferably a
C.sub.1-C.sub.10-alkyl radical.
[0038] Hydrogen atoms present in the a position relative to
aromatic radicals or vinylic groups are, for example, benzylic
hydrogen atoms as in the methyl group (CH.sub.3--C.sub.6H.sub.5) of
toluene or in the methine group
((CH.sub.3).sub.2CH--C.sub.6H.sub.5) of cumene or allylic hydrogen
atoms as in the methylene group (CH.sub.2.dbd.CH--CH.sub.2--CH.s-
ub.3) of 1-butene.
[0039] Unless restricted further, alkyl is a linear, branched or
cyclic radical such as methyl, ethyl, n-propyl, isopropyl, n-butyl,
i-butyl, s-butyl, t-butyl, n-pentyl, n-hexyl, cyclohexyl, n-heptyl
or n-octyl.
[0040] The above-described process of the present invention is
preferably used for preparing substituted indenes of the formula
(I) or (Ia) in which
[0041] R.sup.1 is a linear, branched or cyclic
C.sub.1-C.sub.10-alkyl radical,
[0042] R.sup.2 is a substituted or unsubstituted
C.sub.6-C.sub.18-aryl radical selected from the group consisting of
phenyl, 1-naphthyl, phenanthryl, 3-tert-butylphenyl,
4-tert-butylphenyl, 3,5-di(tert-butyl)phenyl, 4,4'-biphenyl and
3,5-di(phenyl)phenyl,
[0043] R.sup.3-R.sup.5 are each hydrogen,
[0044] X is a chlorine atom,
[0045] M is magnesium monochloride and
[0046] Y is OR.sup.6, where R.sup.6 is a linear, branched or cyclic
C.sub.1-C.sub.10-alkyl radical.
[0047] In the preferred embodiment, the radicals and substituents
can be described in more detail as follows:
[0048] R.sup.1 is a linear, branched or cyclic
C.sub.1-C.sub.10-alkyl radical. Examples of radicals R.sup.1 are
methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl,
n-pentyl, cyclopentyl, n-hexyl, cyclohexyl, n-heptyl, n-octyl and
n-decyl.
[0049] R.sup.2 is a substituted or unsubstituted
C.sub.6-C.sub.18-aryl radical selected from the group consisting of
phenyl, 1-naphthyl, phenanthryl, 3-tert-butylphenyl,
4-tert-butylphenyl, 3,5-di(tert-butyl)phenyl, 4,4'-biphenyl and
3,5-di(phenyl)phenyl. R.sup.2 is particularly preferably phenyl,
1-naphthyl, 4-tert-butylphenyl or 3,5-di(tert-butyl)phenyl.
[0050] Y is OR.sup.6, where R.sup.6 is a linear, branched or cyclic
C.sub.1-C.sub.10-alkyl radical, for example methyl, ethyl,
n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, n-pentyl,
cyclopentyl, n-hexyl, cyclohexyl, n-heptyl, n-octyl or n-decyl.
R.sup.6 is preferably methyl or ethyl.
[0051] Particular preference is given to the process of the present
invention in which the compound of the formula (II) 12
[0052] where the radicals X, R.sup.2, R.sup.3, R.sup.4 and R.sup.5
are as defined above,
[0053] is prepared by coupling of a compound of the formula (VI)
13
[0054] with a compound of the formula (VII)
R.sup.2--X.sup.2 (VII)
[0055] in the presence of a transition metal catalyst, with either
the compound of the formula (VI) or the compound of the formula
(VII) firstly being converted into a corresponding organometallic
compound, in particular a lithium or Grignard compound, and the
coupling product of the formula 14
[0056] is reacted with a halogenating agent and, if desired, the
halogen atoms introduced in this way are subsequently replaced by
other halogen atoms, giving the compound of the formula (II)
[0057] where
[0058] X.sup.1 is halogen, in particular chlorine, bromine or
iodine, preferably chlorine, and
[0059] X.sup.2 is halogen, in particular chlorine, bromine or
iodine, preferably bromine.
[0060] Compounds of the formulae (VI) and (VII) are commercially
available. The compounds of the formula (VI) or (VII) can be
converted into the corresponding organolithium compounds or
Grignard compounds by methods known from the literature, or the
organometallic compounds are in some cases also commercially
available. The synthesis of such Grignard reagents is described,
for example, in Holm, Torkil, J. Chem. Soc. Perkin Trans. 2.1981,
464-467. The synthesis of further organometallic reagents starting
from the compounds of the formulae (VI) and (VII) can be carried
out by standard methods of organometallic chemistry which may be
found, for example, in March, Advanced Organic Chemistry, 4th
edition, 1992, and in the references cited therein.
[0061] The aryl-aryl coupling in the presence of a transition metal
catalyst for the purpose of synthesizing the compound of the
formula (VIII) is known and can be carried out by methods known
from the literature, as described, for example, in Synthesis 1990,
147-148. The transition metal catalysts preferably used in the
coupling reaction are thus also known from the literature and are
generally commercially available.
[0062] As transition metal catalysts, it is in principle possible
to use transition metal complexes of groups 8 to 10 of the Periodic
Table of the Elements, in particular group 10. Particularly useful
catalysts are complexes of nickel or of palladium, in particular
complexes of nickel, for example nickel(II) chloride,
[1,3-bis(diphenylphosphino)propane]nicke- l(II) chloride
(NiCl.sub.2[dppp].sub.2), [1,2-bis(diphenylphosphino)ethane-
]nickel(II) chloride (NiCl.sub.2[dppe].sub.2),
bis(triphenylphosphine)nick- el(II) chloride,
[1,1'-bis(diphenylphosphino)ferrocene]nickel(II) chloride.methylene
chloride adduct. In the case of an arylboronic acid being used in
the coupling reaction instead of an aryllithium or arylmagnesium
compound, particular preference is given to using palladium
complexes as described in WO 98/40331 and the references cited
therein as catalysts.
[0063] The coupling reaction for preparing the compound of the
formula (VIII) is carried out in suitable inert solvents or solvent
mixtures appropriate to the particular reactants, for example
diethyl ether, tetrahydrofuran, toluene, etc., under a protective
gas atmosphere.
[0064] The conversion of the two methyl groups in the compounds of
the formula (VIII) into two halomethyl groups (formula (II)) is in
principle known from the literature and is usually carried out by
free-radical side chain halogenation using brominating agents such
as elemental bromine or N-bromosuccinimide or using chlorinating
reagents such as elemental chlorine or sulfuryl chloride (cf.
March, Advanced Organic Chemistry, 4th edition, 1992, and the
references cited therein).
[0065] The replacement of the halogen radicals X in compounds of
the formula (II) by other halogen radicals X is likewise a method
known from the literature and is described, for example, in March,
Advanced Organic Chemistry, 4th edition, 1992, and the references
cited therein.
[0066] The preparation of the compound of the formula (III) can be
carried out by methods based on procedures known from the
literature, as described in Organometallics 1993, 12, 4398. Apart
from magnesium in the form of turnings or powder, which may, if
appropriate, be corroded on the surface, i.e. activated, by means
of 1,2-dibromoethane, it is also possible to use other
high-activity magnesium sources such as magnesium-anthracene to
produce the compounds of the formula (III) from the compounds of
the formula (II).
[0067] The reaction of the compound of the formula (III) with
compounds of the formula (IV) to form compounds of the formula (V)
is in principle a method known from the literature and can be
carried out using procedures based on those in Organometallics
1993, 12, 4398 or Organometallics 1999, 18, 4147-4155. The
indan-2-ol formed can be dehydrated by standard methods, for
example as described in U.S. Pat. No. 5,770,753, to form the indene
of the formula (I) or (la). As acid catalysts, it is possible to
use, for example, p-toluenesulfonic acid, sulfuric acid,
hydrochloric acid or a strong acid ion exchanger.
[0068] The invention is illustrated by the following nonrestrictive
examples:
[0069] General Procedures:
[0070] The preparation and handling of organometallic compounds
was, unless indicated otherwise, carried out with exclusion of air
and moisture under argon as protective gas (Schlenk technique or
glove box). All anhydrous solvents required were purged with argon
and dried over molecular sieves before use. The .sup.1H NMR spectra
were measured at 400 MHz in CDCl.sub.3. Chromatographic
purifications were carried out using Fluka Silica 60 (230-400
mesh).
EXAMPLE 1
4-tert-Butyl-2',3'-dimethylbiphenyl
[0071] 23.8 g (1.1 eq.) of magnesium (for Grignard reactions from
Aldrich) were suspended in 95 ml of tetrahydrofuran (THF) and
activated by addition of a small amount of iodine. 62.7 g (0.45
mol) of 2,3-dimethylchlorobenzene were subsequently added. To start
the Grignard reaction, a few drops of 1,2-dibromoethane were
carefully added. After the reaction had been started successfully,
the remaining 62.7 g (0.45 mol) of 2,3-dimethylchlorobenzene
diluted with 380 ml of THF were added dropwise at such a rate that
the reaction solution boiled gently. The reaction mixture was
subsequently refluxed until the magnesium had mostly reacted (2
hours). After the reaction mixture had cooled to room temperature,
a further 95 ml of THF were added to the viscous mixture. 190.0 g
(0.89 mol) of p-tert-butylbromobenzene diluted with 190 ml of THF
were placed in a further reaction flask. 1.0 g (1 mol %) of
nickel(II) chloride was added thereto, followed by careful addition
of the Grignard solution. The temperature rose briefly to
80.degree. C. The reaction mixture was stirred at 50-55.degree. C.
for 2 hours. After cooling to room temperature, 190 ml of 2 molar
hydrochloric acid were carefully added. The aqueous phase was
extracted with diethyl ether (3.times.200 ml), the combined organic
phases were dried over magnesium sulfate and the solvent was
removed under reduced pressure. The residue was recrystallized from
boiling ethanol and two crystal fractions were obtained (1st
fraction: 139.3 g, 100% according to GC/2nd fraction: 20.5 g, 96.2%
according to GC). Combined yield: 159.8 g (0.67 mol/75%). .sup.1H
NMR (400 MHz, CDCl.sub.3): .delta.=7.41 ("d", 2H, aromatic), 7.21
("d"<2H, aromat.), 7.14-7.07 (m, 3H, aromat.), 2.33 (s, 3H,
CH.sub.3), 2.16 (s, 3H, CH.sub.3), 1.36 (s, 9H, tert-butyl)
ppm.
EXAMPLE 2
4-tert-Butyl-2',3'-bis(bromomethyl)biphenyl
[0072] 137.2 g (0.58 mol) of 4-tert-butyl-2',3'-dimethylbiphenyl
were dissolved in 576 ml of carbon tetrachloride. 205.1 g (1.15
mol) of N-bromosuccinimide and 1.37 g (8.3 mmol) of AIBN were added
and the mixture was heated quickly to reflux temperature. After the
reaction was complete (3 hours according to thin layer
chromatography), the reaction mixture was cooled to room
temperature and the succinimide which precipitated was removed by
filtration. The filter cake was washed with further carbon
tetrachloride. The combined filtrates were evaporated under reduced
pressure to remove the solvent. 259.5 g of crude product were
obtained. 550 ml of ethanol were added and the mixture was allowed
to stand overnight to crystallize. Since no crystals had
precipitated, a small crystal of the product from a previous
experiment was added to the solution. The product crystallized out
rapidly, and the crystals were separated off by filtration and
washed with ethanol.
[0073] Yield: 179.8 g (0.45 mol/79%/84.4% by GC). .sup.1H NMR (400
MHz, CDCl.sub.3): .delta.=7.45, 7.38, 7.31, 7.21 (4.times.m, 7H,
aromat.), 4.78, 4.61 (2.times.s, 2.times.2H, CH.sub.2Br), 1.36 (s,
9H, tert-butyl) ppm.
EXAMPLE 3
4-tert-Butyl-2',3'-bis(chloromethyl)biphenyl
[0074] 40.0 g (101.0 mmol) of
tert-butyl-2,3-bis(bromomethyl)biphenyl were dissolved in 660 ml of
DMF. 25.7 g (6 eq.) of lithium chloride were added and the reaction
mixture was stirred at room temperature for 24 hours. 500 ml of
water and 300 ml of diethyl ether were subsequently added and the
aqueous phase was extracted with diethyl ether (2.times.200 ml).
The combined organic phases were washed with water (3.times.150 ml)
and saturated sodium chloride solution (1.times.100 ml) and dried
over magnesium sulfate. The solvent was removed under reduced
pressure to give a yellow oil. Crystallization from 200 ml of
ethanol gave 17.9 g of white crystals. The mother liquor was
concentrated under reduced pressure and left to crystallize. A
further 5.5 g of a 2nd crystal fraction were obtained. Combined
yield: 23.4 g (76 mmol/75%/89.5% by GC). .sup.1H NMR (400 MHz,
CDCl.sub.3): .delta.=7.46-7.26 (m, 7H, aromat.), 4.86, 4.67
(2.times.s, 2.times.2H, CH.sub.2Cl), 1.36 (s, 9H, tert-butyl).
EXAMPLE 4
4-(4-tert-Butylphenyl)-2-methyl-1H-indene and
7-(4-tert-butylphenyl)-2-met- hyl-1H-indene
[0075] 8.4 g (20.0 mmol) of magnesium-anthracene 3 THF were
dissolved in 100 ml of THF. A solution of 3.07 g (10.0 mmol) of
tert-butyl-2,3-bis(chloromethyl)biphenyl in 20 ml of THF were added
dropwise at 0.degree. C. over a period of 30 minutes. The reaction
mixture was stirred at room temperature for another 30 minutes. A
sample was taken and hydrolyzed (GC analysis: 60% formation of the
bis-Grignard+formation of oligomers). A solution of 741 mg (1 eq.)
of methyl acetate in 30 ml of THF was added dropwise at 0.degree.
C. over a period of 30 minutes and the reaction mixture was stirred
overnight at room temperature. The reaction mixture was
subsequently added to a saturated solution of ammonium chloride.
The aqueous phase was extracted with diethyl ether (3.times.100
ml). The combined organic phases were dried over magnesium chloride
and the solvent was evaporated under reduced pressure. GC analysis
of the crude product (7.28 g) showed 15% of the desired indanol
together with anthracene and further by-products. Anthracene was
removed by column chromatography using heptane as eluant, and the
indanol was eluted using a 1:1 mixture of methylene
chloride/ethanol. The yellow oil obtained after removal of the
solvents (2.3 g, 64.4% of indanol according to GC) was dissolved in
40 ml of toluene and refluxed in the presence of 5 mol % of
p-toluenesulfonic acid for 1.5 hours on a water separator. The
organic phase was washed with saturated sodium hydrogen carbonate
solution (1.times.40 ml) and dried over magnesium sulfate. Removal
of the solvent and purification by column chromatography gave 0.72
g (2.8 mmol/28%) of a 1:1 mixture of the desired indenes (93% by
GC). .sup.1H NMR (400 MHz, CDCl.sub.3): .delta.=7.48-7.14 (m,
aromat.), 6.72, 6.54 (2.times.s, .dbd.C--H), 3.42, 3.38 (2.times.s,
CH.sub.3), 2.16 ("s", CH.sub.2), 1.39 ("s", tert-butyl) ppm.
EXAMPLE 5
4-(4-tert-butylphenyl)-2-methylindan-2-ol
[0076] 633 mg (26 mmol, 4 eq.) of Mg powder (50 mesh/Aldrich) were
dried under reduced pressure with the aid of a hair dryer. 10 ml of
THF and 10 drops of 1,2-dibromoethane were added. The mixture was
heated to reflux until gas evolution took place and the activation
was complete. The solvent was removed under reduced pressure and 10
ml of fresh THF were added. A solution of 2.0 g (6.5 mmol) of
tert-butyl-2,3-bis(chloromethyl)- biphenyl in 120 ml of THF was
added and the suspension was stirred vigorously at room temperature
for 3 hours. Stirring was continued overnight and the slightly
greenish turbid solution obtained was filtered to remove excess
magnesium. The filtrate was cooled to -78.degree. C. and a solution
of 482 mg (6.51 mol) of methyl acetate in 60 ml of THF was added
dropwise over a period of 1 hour. The reaction solution was warmed
to 0.degree. C. over a period of 2 hours. 80 ml of water were
subsequently added and the solution was concentrated under reduced
pressure. To dissolve the magnesium salts, 3 ml of concentrated
hydrochloric acid were added and the aqueous phase was extracted
with methylene chloride (3.times.50 ml). The combined organic
phases were dried over magnesium sulfate, and the solvent was
subsequently removed under reduced pressure. The product was
purified by column chromatography, with the nonpolar by-products
being separated off using a heptane/dichloromethane mixture and the
product being eluted with pure dichloromethane, giving a yellow
product. Yield: 0.64 g (2.28 mmol/35%/94.5% by GC). .sup.1H NMR
(400 MHz, CDCl.sub.3): .delta.=7.43-7.22 (m, 7H, aromat.), 3.08 (m,
4H, CH.sub.2), 1.48 (s, 3H, CH.sub.3), 1.35 (s, 9H, tert-butyl)
ppm.
EXAMPLE 6
4-(4-tert-butylphenyl)-2-isopropylindan-2-ol
[0077] 633 mg (26 mmol, 4 eq.) of Mg powder (50 mesh/Aldrich) were
dried under reduced pressure with the aid of a hair dryer. 10 ml of
THF and 10 drops of 1,2-dibromoethane were added. The mixture was
heated to reflux until gas evolution took place and the activation
was complete. The solvent was removed under reduced pressure and 10
ml of fresh THF were added. A solution of 2.0 g (6.5 mmol) of
tert-butyl-2,3-bis(chloromethyl)- biphenyl in 120 ml of THF was
added and the suspension was stirred vigorously at room temperature
for 3 hours. Stirring was continued overnight and the slightly
greenish turbid solution obtained was filtered to remove excess
magnesium. The filtrate was cooled to -78.degree. C. and a solution
of 665 mg (6.51 mol) of methyl isobutyrate in 60 ml of THF was
added dropwise over a period of 1 hour. The reaction solution was
warmed to 0.degree. C. over a period of 2 hours. 80 ml of water
were subsequently added and the solution was concentrated under
reduced pressure. To dissolve the magnesium salts, 3 ml of
concentrated hydrochloric acid were added and the aqueous phase was
extracted with methylene chloride (3.times.50 ml). The combined
organic phases were dried over magnesium sulfate, and the solvent
was subsequently removed under reduced pressure. The product was
purified by column chromatography, with the nonpolar by-products
being separated off using a heptane/dichloromethane mixture and the
product being eluted with pure dichloromethane, giving a yellow
product. Yield: 0.66 g (2.14 mmol/33% 96% by GC). .sup.1H NMR (400
MHz, CDCl.sub.3): .delta.=7.41-7.21 (m, 7H, aromat.), 3.18-2.91 (m,
4H, CH.sub.2), 1.92 (m, 1H, CH), 1.36 (s, 9H, tert-butyl), 1.02 (t,
6H, CH.sub.3) ppm.
* * * * *